Association Between the Duration of Periodontitis and Increased Cardiometabolic Risk Factors: A 9-Year Cohort Study

Abstract

Background:

Epidemiological studies have reported that periodontitis and cardiometabolic disease such as cardiovascular disease and type 2 diabetes are associated; however, there have been very few prospective cohort studies on this topic. Therefore, we conducted a 9-year follow-up study to examine the relationship between the duration of periodontitis and cardiometabolic risk factors, including hypertension, hyperglycemia, dyslipidemia, and obesity.

Methods:

The study participants comprised 572 adult industrial workers (417 men and 155 women; mean age, 37.4 years) who had undergone annual medical and dental health examinations from 2003 to 2012; the evaluation of the four cardiometabolic risk factors in 2003 revealed normal values in all the participants. We investigated the relationship between the cumulative duration of the presence of periodontal pockets, which is a major symptom of periodontitis, and the presence of cardiometabolic risk factors after 9 years using multiple logistic regression analysis.

Results:

The odds ratio (OR) for the presence of ≥1 cardiometabolic risk factor in participants with a cumulative duration of periodontal pockets for ≥6 years was significantly higher than that in participants without pockets. The ORs for the onset of obesity, hypertension, dyslipidemia, and hyperglycemia were higher in participants with a cumulative duration of periodontal pockets for ≥6 years than those in participants without pockets or in participants with a cumulative duration of periodontal pockets for ≤5 years, and all the differences, except dyslipidemia, were significant.

Conclusions:

Chronic periodontitis was significantly associated with having cardiometabolic risk factors during the 9-year observation period, suggesting that the risk of cardiometabolic disease might increase in people who have untreated periodontitis.

Introduction

Metabolic syndrome, which includes hypertension, hyperglycemia, and dyslipidemia, is a medical condition probably arising from visceral fat accumulation (central obesity). The various components of metabolic syndrome lead to a higher risk of cardiometabolic disease such as cardiovascular disease^1,2 and type 2 diabetes.^3,4 Periodontitis is a chronic inflammatory disease in which periodontal tissues are damaged owing to infection with Gram-negative anaerobic bacteria.^5,6 Increased blood levels of the markers of inflammation, such as C-reactive protein, tumor necrosis factor α, and interleukin 6, have been reported in patients with periodontitis,^6
–8 indicating that periodontitis is a mild chronic inflammatory disease with systemic effects. Epidemiological studies evaluating the relationship between periodontitis and metabolic syndrome have been conducted among Japan community residents,⁹ northern Jordan adults,¹⁰ and Chinese adults,¹¹ as well as through the analysis of the results of the U.S. National Health and Nutrition Examination Survey III.¹² In previous cross-sectional and prospective 4-year follow-up cohort studies involving Japanese adult employees, we reported that the risk for metabolic syndrome was high in patients with periodontitis.^13,14

The association between cardiometabolic risk factors and metabolic syndrome is well documented. Obesity can contribute to the development of hypertension, dyslipidemia, and hyperglycemia,^15,16 which in turn contribute to many complications of cardiometabolic disease.^1

–4,17 In our previous 4-year cohort study, we reported an association between the positive conversion of hypertension, dyslipidemia, and obesity and the existence of periodontal pockets, which is a major symptom of periodontitis, whereas hyperglycemia was not associated.¹⁴ This was probably because the study involved few participants who were negative for all these disorders at baseline and those who developed hyperglycemia after 4 years. Thus, we considered that extending the follow-up period might allow accurate observation of the onset of chronic diseases, including hyperglycemia. In fact, a cohort study¹⁸ with an observation period of longer than 4 years and an interventional study¹⁹ have identified an association between diabetes and periodontitis.

In the present study, we conducted a 9-year follow-up to examine whether periodontitis and increased risk of cardiometabolic disease were associated. We examined the relationship between the duration of periodontitis and the onset of hypertension, dyslipidemia, hyperglycemia, and obesity as cardiometabolic risk factors using data on the cumulative duration of the existence of periodontal pockets.

Materials and Methods

Participants

Participants in this study were industrial workers of a household products manufacturing company in Tokyo, Japan. These participants had undergone annual health and dental examinations from 2003 to 2012, which were conducted independently by a health insurance association. In 2003, 99.9% of all the workers had undergone systemic medical examinations, 84.2% had undergone dental examinations, and 2904 had undergone both. A total of 1119 workers had undergone annual examinations from 2003 to 2012. Written informed consents were obtained from all the workers who participated in the present study. There were 592 (431 men and 161 women) participants who did not have cardiometabolic risk factors, including obesity, hypertension, dyslipidemia, and hyperglycemia (criteria of these disorders are described below) in 2003 (baseline). We excluded 10 participants who did not respond to the self-administered questionnaire. The final study population for the analysis comprised 572 participants (417 men and 155 women; mean age, 37.4 years). The study was approved by the Ethics Committee of Nihon University School of Dentistry.

Evaluation of periodontitis

We used the World Health Organization (WHO) Community Periodontal Index (CPI) criteria to assess the presence of periodontitis.²⁰ For CPI measurements, 10 representative teeth in 6 sextants were examined by a dental hygienist under the supervision of dentists. Oral examination was performed using standard WHO probes after calibration of the pressure (<20 g) of the probe using a sensor probe. The participants were categorized into two groups: those with a CPI score of ≤2 (no periodontal pockets) and those (including a minimum of one sextant) with a CPI score of ≥3 (periodontal pockets of ≥4 mm).

Systemic examination

Blood pressure was measured with the participant in a sitting position using an automatic hemomanometer. The participants were asked to fast overnight starting at 9.00 p.m., and blood samples from an arm vein were collected the following morning. Triglyceride, high-density lipoprotein cholesterol, and fasting blood glucose levels were measured in these samples. To evaluate the presence of obesity, we calculated the body mass index from the height and body weight of each study participant. The presence of hypertension, dyslipidemia, and hyperglycemia was defined as per the diagnostic criteria for metabolic disorders in Japan.^21,22 The diagnostic values of these disorders were as follows: for hypertension, systolic blood pressure of ≥130 mmHg or a diastolic blood pressure of ≥85 mmHg; dyslipidemia, serum triglyceride level of ≥150 mg/dL or serum high-density lipoprotein cholesterol level of <40 mg/dL; and hyperglycemia, fasting blood glucose level of ≥110 mg/dL. In terms of obesity, a body mass index of ≥25 kg/m² was considered to indicate a metabolic disorder.

Survey on lifestyle (questionnaire)

The participants were surveyed regarding lifestyle, cigarette smoking habits, alcohol consumption habits, and body weight control using a self-administered questionnaire at the time of periodic health examinations. The following questions were used for the analysis: “Do you smoke?,” “Do you drink alcohol?,” and “Do you maintain a healthy body weight?” Smoking habits and body weight control were assessed from “Yes” or “No” answers. Alcohol consumption habits were assessed using answers coded as “Does not drink alcohol,” “Drinks alcohol 2 or 3 times a week,” “Drinks alcohol 4 or 5 times a week,” and “Drinks alcohol every day.” Participants who selected “Does not drink alcohol” were regarded as nondrinkers, whereas the others were regarded as drinkers.

Statistical analyses

We used multiple logistic regression analysis to evaluate the relationship between periodontitis and the number of positive components (or the components that changed to positive) of cardiometabolic risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) after 9 years. The positivity of each risk factor after 9 years was the dependent variable, and the independent variable was the duration of existence of periodontal pockets, which indicated cumulative exposure.²³ The odds ratios (ORs) and confidence intervals were calculated with adjustments for age, sex, cigarette smoking, alcohol consumption, and maintenance of a healthy body weight.^24
–26 JMP software (version 9.0; SAS Institute, Tokyo, Japan) was used for statistical analyses, and a level of <5% was considered significant.

Results

Proportion of participants with periodontal pockets

At baseline, 89 participants (15.6%) had periodontal pockets, and 483 (84.4%) did not have periodontal pockets. The distribution of participants according to the cumulative duration of periodontal pockets is shown in Figure 1. The number of participants who never had periodontal pockets during the observation period (cumulative duration: 0 year) was markedly higher than the number of participants who had periodontal pockets (cumulative duration: 1–10 years), and the number of participants with such pockets decreased as a function of cumulative duration. In the subsequent analysis, we divided the participants into the following three groups based on the cumulative duration of periodontal pockets: one that included participants with a cumulative duration of 0 (n = 252, 44.1%), another that included those with a cumulative duration of ≤5 years (n = 249, 43.5%), and the third that included those with a cumulative duration of ≥6 years (n = 71, 12.4%). Thus, we divided the participants with periodontal pockets into two groups based on the median cumulative duration (5 years). The factors in the lifestyle survey were also classified into three grades based on the cumulative duration.

FIG. 1.

Distribution of participants according to the cumulative duration of periodontal pockets.

Proportion of participants with cardiometabolic risk factors after 9 years

After 9 years, there were no cardiometabolic risk factors in 403 (70.4%) participants and 1, 2, and ≥3 risk factors in 128 (22.4%), 37 (6.5%), and 4 (0.7%) participants, respectively. The proportion of participants who had one or more cardiometabolic risk factors after 9 years was higher in the group with a cumulative duration of periodontal pockets for ≥6 years (45.1%) than in the group with a cumulative duration of periodontal pockets for ≤5 years (33.7%) or in the group without periodontal pockets (21.0%).

Association between the number of cardiometabolic risk factors after 9 years and cumulative duration of periodontal pockets

Table 1 shows the association between the number of cardiometabolic risk factors after 9 years and the cumulative duration of the presence of periodontal pockets. With one risk factor, the OR was 1.8 (95% confidence interval [CI], 1.1–2.8) in the group with a cumulative duration of periodontal pockets for ≤5 years and 2.1 (95% CI, 1.1–4.1) in the group with a cumulative duration of periodontal pockets for ≥6 years relative to the group without periodontal pockets. Moreover, there were significant differences between the groups with periodontal pockets and the group without periodontal pockets. When having ≥2 risk factors, the OR was 1.4 (95% CI, 0.6–3.3) in the group with a cumulative duration of periodontal pockets for ≤5 years and 4.1 (95% CI, 1.6–10.6) in the group with a cumulative duration of periodontal pockets for ≥6 years relative to the group without periodontal pockets; this was significant for the group with a duration of periodontal pockets for ≥6 years.

Table 1.

Association Between the Number of Cardiometabolic Risk Factors in 2012 and Cumulative Exposure to Periodontitis During the 9-Year Study Period (2003–2012)

	No. of participants (%) in 2012				OR (95% CI)
	No risk factor n = 403 (70.4)	One risk factor n = 128 (22.4)	Two risk factors n = 37 (6.5)	Three risk factors n = 4 (0.7)	One risk factor	Two or more risk factors
Periodontal pockets
Without pocket	199 (79.0)	41 (16.3)	12 (4.7)	0 (0.0)	1	1
With pocket (≤5 years)	165 (66.3)	67 (26.9)	13 (5.2)	4 (1.6)	1.8 (1.1–2.8)^*	1.4 (0.6–3.3)
With pocket (≥6 years)	39 (54.9)	20 (28.2)	12 (16.9)	0 (0.0)	2.1 (1.1–4.1)^*	4.1 (1.6–10.6)^**
Smoking habit
No	295 (74.9)	78 (19.8)	19 (4.8)	2 (0.5)	1	1
≤5 Years	33 (60.0)	14 (25.5)	6 (10.9)	2 (3.6)	1.4 (0.7–2.7)	3.3 (1.2–8.6)^*
≥6 Years	75 (61.0)	36 (29.3)	12 (9.7)	0 (0.0)	1.5 (0.9–2.5)	1.4 (0.6–3.2)
Drinking habit
No	118 (75.1)	29 (18.5)	8 (5.1)	2 (1.3)	1	1
≤5 Years	47 (70.1)	17 (25.4)	3 (4.5)	0 (0.0)	1.4 (0.7–2.9)	0.6 (0.1–2.2)
≥6 Years	238 (68.4)	82 (23.6)	26 (7.5)	2 (0.5)	1.0 (0.6–1.7)	0.9 (0.4–2.3)
Excessive weight gain
No	177 (78.7)	41 (18.2)	7 (3.1)	0 (0.0)	1	1
≤5 Years	145 (69.7)	45 (21.6)	17 (8.2)	1 (0.5)	1.3 (0.8–2.1)	3.5 (1.4–9.6)^**
≥6 Years	81 (58.3)	42 (30.2)	13 (9.3)	3 (2.2)	2.4 (1.4–4.0)^**	5.7 (2.2–16.4)^**
Age
<40 Years	301 (74.0)	82 (20.1)	22 (5.4)	2 (0.5)	1	1
≥40 Years	102 (61.8)	46 (27.9)	15 (9.1)	2 (1.2)	1.5 (1.0–2.4)	2.2 (1.0–4.5)^*
Gender
Female	126 (81.3)	22 (14.2)	6 (3.9)	1 (0.6)	1	1
Male	277 (66.5)	106 (25.4)	31 (7.4)	3 (0.7)	1.8 (1.1–3.3)^*	1.5 (0.6–4.1)

P < 0.01, ^* P < 0.05.

Association between each cardiometabolic risk factors after 9 years and cumulative duration of periodontal pockets

The indicators of obesity, hypertension, dyslipidemia, and hyperglycemia exceeded the normal limits after 9 years in 46 (8.0%), 100 (17.5%), 58 (10.1%), and 10 (1.7%) participants, respectively. The associations between the positive conversion of obesity, hypertension, dyslipidemia, and hyperglycemia after 9 years and the presence of periodontal pockets are shown in Tables 2 –5. The OR of obesity was 2.6 (95% CI, 1.3–5.6) in the group with a cumulative duration of periodontal pockets for ≤5 years and 3.0 (95% CI, 1.1–8.2) in the group with a cumulative duration of periodontal pockets for ≥6 years relative to the group without periodontal pockets during the 9-year period; these data reflected significant differences between the groups (P < 0.05). The OR of hypertension was 1.5 (95% CI, 0.9–2.4) in the group with a cumulative duration of periodontal pockets for ≤5 years and 2.2 (95% CI, 1.1–4.3) in the group with a cumulative duration of periodontal pockets for ≥6 years relative to the group without periodontal pockets; there was a significant difference in the group with a cumulative duration of periodontal pockets for ≥6 years (P < 0.05). No participant in the group without periodontal pockets had hyperglycemia after 9 years; therefore, the OR in the group with a cumulative duration of periodontal pockets for ≥6 years was calculated relative to the group without periodontal pockets during the 9-year period and to the group with a cumulative duration of periodontal pockets for ≤5 years. The OR was 6.4 (95% CI, 1.5–27.5), which reflected a significant difference between the two groups (P < 0.05). The ORs for dyslipidemia were slightly higher in both the groups with periodontal pockets than in the group without periodontal pockets; however, this difference was not significant.

Table 2.

Association Between Obesity in 2012 and Cumulative Exposure to Periodontitis During the 9-Year Study Period (2003–2012)

	No. of participants (%) in 2012
	Nonobese n = 526 (92.0)	Obese n = 46 (8.0)	OR (95% CI)
Periodontal pockets
Without pocket	240 (95.2)	12 (4.8)	1
With pocket (≤5 years)	223 (89.6)	26 (10.4)	2.6 (1.3–5.6)^**
With pocket (≥6 years)	63 (88.7)	8 (11.3)	3.0 (1.1–8.2)^*
Smoking habit
No	367 (93.2)	27 (6.8)	1
≤5 Years	48 (87.3)	7 (12.7)	2.3 (0.8–5.8)
≥6 Years	111 (90.2)	12 (9.8)	1.2 (0.5–2.5)
Drinking habit
No	144 (91.7)	13 (8.3)	1
≤5 Years	59 (88.1)	8 (11.9)	1.7 (0.6–4.6)
≥6 Years	323 (92.8)	25 (7.2)	0.8 (0.4–1.8)
Excessive weight gain^a
≤5 Years	412 (95.2)	21 (4.8)	1
≥6 Years	114 (82.0)	25 (18.0)	4.7 (2.5–9.1)^**
Age
<40 Years	375 (92.1)	32 (7.9)	1
≥40 Years	151 (91.5)	14 (8.5)	1.1 (0.5–2.2)
Gender
Female	142 (91.6)	13 (8.4)	1
Male	384 (92.1)	33 (7.9)	0.8 (0.4–1.7)

P < 0.01, ^* P < 0.05.

Participants were categorized into two groups because none of the subjects, who lacked awareness regarding excessive weight gain, as noted in the lifestyle survey, was obese during the 9-year study period.

Table 3.

Association Between Hypertension in 2012 and Cumulative Exposure to Periodontitis During the 9-Year Study Period (2003–2012)

	No. of participants (%) in 2012
	Nonhypertensive n = 472 (82.5)	Hypertensive n = 100 (17.5)	OR (95% CI)
Periodontal pockets
Without pocket	221 (87.7)	31 (12.3)	1
With pocket (≤5 years)	201 (80.7)	48 (19.3)	1.5 (0.9–2.4)
With pocket (≥6 years)	50 (70.4)	21 (29.6)	2.2 (1.1–4.3)^*
Smoking habit
No	334 (84.8)	60 (15.2)	1
≤5 Years	41 (74.6)	14 (25.4)	1.6 (0.8–3.1)
≥6 Years	97 (78.9)	26 (21.1)	1.2 (0.7–2.0)
Drinking habit
No	132 (84.1)	25 (15.9)	1
≤5 Years	57 (85.1)	10 (14.9)	0.9 (0.4–1.9)
≥6 Years	283 (81.3)	65 (18.7)	0.9 (0.5–1.5)
Excessive weight gain
No	191 (84.9)	34 (15.1)	1
≤5 Years	173 (83.2)	35 (16.8)	1.1 (0.6–1.9)
≥6 Years	108 (77.7)	31 (22.3)	1.8 (1.0–3.2)^*
Age
<40 Years	351 (86.2)	56 (13.8)	1
≥40 Years	121 (73.3)	44 (26.7)	2.1 (1.3–3.4)^**
Gender
Female	140 (90.3)	15 (9.7)	1
Male	332 (79.6)	85 (20.4)	2.0 (1.1–4.0)^*

P < 0.01, ^* P < 0.05.

Table 4.

Association Between Dyslipidemia in 2012 and Cumulative Exposure to Periodontitis During the 9-Year Study Period (2003–2012)

	No. of participants (%) in 2012
	Nondyslipidemia n = 514 (89.9)	Dyslipidemia n = 58 (10.1)	OR (95% CI)
Periodontal pockets
Without pocket	230 (91.3)	22 (8.7)	1
With pocket (≤5 years)	223 (89.6)	26 (10.4)	1.1 (0.6–2.0)
With pocket (≥6 years)	61 (85.9)	10 (14.1)	1.3 (0.5–3.0)
Smoking habit
No	365 (92.6)	29 (7.4)	1
≤5 Years	46 (83.6)	9 (16.4)	1.8 (0.8–4.0)
≥6 Years	103 (83.7)	20 (16.3)	2.0 (1.0–3.7)^*
Drinking habit
No	146 (93.0)	11 (7.0)	1
≤5 Years	62 (92.5)	5 (7.5)	0.9 (0.3–2.7)
≥6 Years	306 (87.9)	42 (12.1)	1.2 (0.6–2.6)
Excessive weight gain
No	207 (92.0)	18 (8.0)	1
≤5 Years	187 (89.9)	21 (10.1)	1.2 (0.6–2.4)
≥6 Years	120 (86.3)	19 (13.7)	1.6 (0.8–3.3)
Age
<40 Years	366 (89.9)	41 (10.1)	1
≥40 Years	148 (89.7)	17 (10.3)	1.0 (0.5–1.8)
Gender
Female	150 (96.8)	5 (3.2)	1
Male	364 (87.3)	53 (12.7)	3.4 (1.4–10.3)^**

P < 0.01, ^* P < 0.05.

Table 5.

Association Between Hyperglycemia in 2012 and Cumulative Exposure to Periodontitis During the 9-Year Study Period (2003–2012)

	No. of participants (%) in 2012
	Nonhyperglycemic n = 562 (98.3)	Hyperglycemic n = 10 (1.7)	OR (95% CI)
Periodontal pockets^a
With pocket (≤5 years)	496 (99.0)	5 (1.0)	1
With pocket (≥6 years)	66 (93.0)	5 (7.0)	6.4 (1.5–27.5)^*
Smoking habit
No	388 (98.5)	6 (1.5)	1
≤5 Years	53 (96.4)	2 (3.6)	6.1 (0.7–45.2)
≥6 Years	121 (98.4)	2 (1.6)	1.1 (0.1–5.9)
Drinking habit^b
≤5 Years	222 (99.1)	2 (0.9)	1
≥6 Years	340 (97.7)	8 (2.3)	3.8 (0.8–29.2)
Excessive weight gain
No	223 (99.1)	2 (0.9)	1
≤5 Years	202 (97.1)	6 (2.9)	3.6 (0.7–27.2)
≥6 Years	137 (98.6)	2 (1.4)	2.7 (0.3–26.3)
Age
<40 Years	404 (99.3)	3 (0.7)	1
≥40 Years	158 (95.8)	7 (4.2)	4.4 (1.1–22.5)^*
Gender
Female	151 (97.4)	4 (2.6)	1
Male	411 (98.6)	6 (1.4)	0.2 (0.0–0.9)^*

P < 0.05.

Participants were categorized into two groups because no subject in the group without periodontal pockets had hyperglycemia during the 9-year study period.

Participants were categorized into two groups because no subject in the group that had consumed alcohol for a maximum of 5 years had hyperglycemia during the 9-year study period.

Discussion

We conducted a 9-year follow-up study involving participants without obesity, hypertension, dyslipidemia, and hyperglycemia and determined whether periodontitis influenced development of those disorders. After 9 years, 8.0%, 17.5%, 10.1%, and 1.7% of our participants had obesity, hypertension, dyslipidemia, and hyperglycemia, respectively. Our previous study¹² showed that 7.1%, 13.7%, 6.7%, and 1.0% of participants developed obesity, hypertension, dyslipidemia, and hyperglycemia, respectively, after 4 years. Thus, the proportion of participants who had developed these disorders at the end of the follow-up period was higher in the present study than in the previous study. These findings indicate that extension of the observation period might reveal a higher rate of onset of each chronic disorder.

Periodontitis induces pathological changes in the periodontal tissue, such as apical migration of the junctional epithelium,²⁷ destruction of connective tissue,²⁸ and osteoclastic bone resorption.²⁹ Because of these changes, periodontal pockets increase in depth. Periodontitis involves both static and active phases, and appropriate professional and/or personal care reduces its symptoms and the depth of periodontal pockets.^30,31 Therefore, the severity of periodontitis is not constant. However, previous cohort studies have evaluated periodontitis based on the results of the examinations at baseline, and the changes in periodontal pockets during the observation period were not considered.¹⁴ In this study, the cumulative duration of the existence of periodontal pockets was incorporated in the epidemiological analysis. Consequently, the ORs of positive conversion of obesity, hypertension, dyslipidemia, and/or hyperglycemia after 9 years were higher in participants with a cumulative duration of periodontal pockets for ≥6 years than in those with a cumulative duration of periodontal pockets for ≤5 years (Table 1). These results indicate that the presence of periodontitis for a prolonged period might increase the risk of cardiometabolic disease.

In the present study, the OR of obesity was 2.6 (95% CI, 1.3–5.6) in participants with a cumulative duration of periodontal pockets for ≤5 years, and it was 3.0 (95% CI, 1.1–8.2) in those with a cumulative duration of periodontal pockets for ≥6 years, reflecting a statistically significant difference (P < 0.05). When we did not consider the change in the existence of periodontal pockets and performed the analysis based on the existence of periodontal pockets at baseline alone, there was no significant association between the presence of obesity after 9 years and the existence of periodontal pockets (data not shown). These results suggest that the effect of periodontitis on the onset of obesity during the observation period was accurately evaluated as cumulative exposure, indicating a significant association between obesity and periodontitis.

No participants in the group without periodontal pockets throughout the 9-year period of the present study had hyperglycemia after 9 years. Therefore, we divided the participants into two groups as follows: a group with a cumulative duration of periodontal pockets for ≤5 years and a group with a cumulative duration of periodontal pockets for ≥6 years, and conducted a logistic regression analysis. The results showed that the proportion of participants who developed hyperglycemia was significantly higher in the latter group (OR, 6.4). In our previous study,¹² the number of participants who developed hyperglycemia after 4 years was very low, and there was no relationship between periodontitis and hyperglycemia. In the present study, the 9-year follow-up period might have allowed the observation of a certain number of cases of hyperglycemia, thus clarifying the association between periodontitis and hyperglycemia.

In the present study, there was no significant association between dyslipidemia and periodontitis, whereas our previous 4-year cohort study found a significant association between the two factors.¹⁴ When the ORs for elevated triglyceride and reduced high-density lipoprotein cholesterol were determined separately, both were slightly higher in participants with periodontal pockets than in participants without periodontal pockets; however, this difference was not significant (data not shown). In the National Health and Nutrition Survey, 2006,³² the Ministry of Health, Labour and Welfare in Japan estimated that ∼14 million individuals in Japan were suspected to have dyslipidemia. They also estimated that 10.5% of this group had taken cholesterol-lowering medications, which lower the serum lipid level.³³ We did not consider medication use in the present study, because the participants at baseline consisted of healthy occupational adults. While planning this longitudinal study, we did not predict the rapid spread of medication use for dyslipidemia in Japan during the observation period, although drug therapy may have had an effect on dyslipidemia.

We found a significant association between periodontitis and the onset of hypertension in both our present (9-year follow-up) and previous (4-year follow-up) studies.¹⁴ Thus, hypertension was the only metabolic component significantly associated with periodontitis in both cohort studies. These results indicate that hypertension might be more sensitive to periodontitis than other cardiometabolic risk factors.

Periodontitis is a mild chronic inflammatory disease^6
–8 caused by Gram-negative anaerobic bacteria existing in periodontal pockets. A recent study suggested that macrophages are activated by the endotoxins of periodontal pathogens, which aggregate in adipose tissue, enhance adipocytokine production, and exacerbate inflammatory responses.³⁴ Another study hypothesized that swallowing periodontal pathogenic bacteria present in the oral cavity, namely, morbid oral bacteria that differ from enteric bacteria, may affect the balance of enteric bacteria, thereby enhancing intestinal permeability and making it possible for endotoxins to invade the intestines and cause mild persistent inflammation in various organs and tissues by spreading through the blood.³⁵ In the present study, the OR of having cardiometabolic risk factors after 9 years was lower in participants with a cumulative duration of periodontal pockets for ≤5 years than in participants with a cumulative duration of periodontal pockets for ≥6 years. The previous findings and our present results indicate that a mild chronic inflammatory state was maintained longer in participants with a long duration (more than 6 years) of periodontitis than in those with a short duration (within 5 years); therefore, the risk of obesity, hypertension, and hyperglycemia was increased in the former participants. Moreover, the results of the present study indicate that these disorders decreased when the periodontal pocket duration was short. Hence, prevention of periodontitis may contribute toward prevention of cardiometabolic disease.

This study has some limitations. Both periodontitis and cardiometabolic risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) are lifestyle-related diseases. Several lifestyle-associated factors that have not been clarified but can affect the onset of both diseases may have acted as confounding factors. Therefore, it is difficult to estimate the impact of periodontitis on the onset of obesity, hypertension, dyslipidemia, and hyperglycemia based on the results of this study alone. An interventional study may be able to determine the effects of treatment of periodontitis on the prevention of these disorders. Another analytical approach, such as an experimental study using animal models or cultured cells, may be necessary to determine the true impact of periodontitis on the onset of cardiometabolic disease.

Conclusion

The results of this 9-year cohort study demonstrate that cardiometabolic risk factors are highest in individuals with a long cumulative duration of periodontal pockets, suggesting that the risk of cardiometabolic disease may increase in people who have periodontitis and in those who leave it untreated for a prolonged period.

Footnotes

Acknowledgments

This study was supported by Grants-in Aid for Scientific Research (C) (nos. 24592842 and 25462942) from the Japanese Society for the Promotion of Science; the Promotion and Mutual Aid Corporation for Private Schools of Japan; the Sato Fund and the Uemura Fund, the Nihon University School of Dentistry; a grant from the Dental Research Center, the Nihon University School of Dentistry; and a Nihon University Multidisciplinary Research Grant (2014–2015).

Author Disclosure Statement

No conflicting financial interests exist.

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